Alpha-Ketoglutarate
Alpha-Ketoglutarate (AKG; umbrella record)
Evidence & Status
- Preliminary / Experimental
- Preliminary
At a Glance
Endogenous Krebs-cycle metabolite. The cited longevity study used Ca-AKG in mice; no human lifespan extension has been established.
Plain English
AKG is a molecule involved in normal cellular energy metabolism. This record is intentionally broad, so it separates the free molecule from Ca-AKG and other AKG salts rather than treating them as interchangeable. The cited lifespan research was done in mice given Ca-AKG. A human report discussed an AKG-based product, but it was retrospective, used a multi-ingredient formulation, and measured a biological-age biomarker rather than lifespan. That does not show that AKG alone reverses aging or extends human lifespan.
Overview
Alpha-ketoglutarate (AKG), also called 2-oxoglutarate, is an endogenous Krebs-cycle metabolite. This umbrella record distinguishes free AKG chemistry, calcium alpha-ketoglutarate (Ca-AKG), and other salts such as arginine AKG; they are not chemically or formulation-equivalent. The displayed molecular-weight value of 146.1 refers to free AKG/alpha-ketoglutaric acid, not Ca-AKG. The cited lifespan and morbidity findings were reported in C57BL/6 mice given Ca-AKG and do not establish human lifespan benefit or benefit for every AKG formulation. A separate retrospective report evaluated a multi-ingredient Ca-AKG-based Rejuvant formulation and a DNA-methylation-age endpoint; it does not establish that isolated AKG or isolated Ca-AKG reverses aging. AKG is marketed as a dietary-supplement ingredient, not an FDA-approved treatment represented by this record.
Research Summary
A cited Cell Metabolism study reported lifespan, healthspan, and morbidity findings in C57BL/6 mice administered Ca-AKG. It is preclinical evidence for that calcium salt and cannot establish human longevity benefit or effects of free AKG or other salts. A separate retrospective analysis of 42 individuals using a multi-ingredient Ca-AKG-based Rejuvant formulation reported changes in a DNA-methylation-age measure after an average of seven months; its formulation, retrospective design, and biomarker endpoint do not establish that isolated AKG reverses aging or extends lifespan. The ABLE publication describes a randomized placebo-controlled sustained-release Ca-AKG protocol with aging-biomarker endpoints; it is a protocol, not efficacy results.
Research Areas
- Longevity
- Epigenetic aging
- Metabolic health
- Cellular energy metabolism
- Krebs cycle
- TET enzyme activity
Safety & Risks
Serious Risks
- The Ca-AKG mouse findings do not establish efficacy for free AKG, other AKG salts, or humans
- The retrospective Rejuvant report studied a multi-ingredient AKG-based formulation and a DNA-methylation-age endpoint; it does not establish isolated AKG reversal of aging
- Human lifespan extension has not been established
- Commercial supplement composition can vary by exact formulation
Reported Side Effects
- Formulation-specific human safety evidence remains limited
- Long-term human safety is not established by the evidence represented here
Legal Status by Region
- United States
- Marketed as a dietary-supplement ingredient; not an FDA-approved treatment represented by this record.
- United Kingdom
- Jurisdiction-specific status is not assessed in this reference.
- Australia
- Jurisdiction-specific status is not assessed in this reference.
- Canada
- Jurisdiction-specific status is not assessed in this reference.
Citations & Sources
- Alpha-Ketoglutarate, an Endogenous Metabolite, Extends Lifespan and Compresses Morbidity in Aging Mice.
Cell Metabolism · 2020
PMID 32877690 · DOI 10.1016/j.cmet.2020.08.004
- Rejuvant®, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging, after an average of 7 months of use, in the TruAge DNA methylation test.
Aging · 2021
PMID 34847066 · DOI 10.18632/aging.203736
- Alpha-ketoglutarate supplementation and BiologicaL agE in middle-aged adults (ABLE)-intervention study protocol.
GeroScience · 2023
PMID 37217632 · DOI 10.1007/s11357-023-00813-6